This is one of a fairly large number of studies, including randomized trials, supporting the use of antiretroviral directly observed therapy (DOT) programs to improve adherence among difficult to reach populations and drug users,(1, 2, 3) including a systematic review;(4) and evaluations of DOT in methadone clinics.(5-8) However, this study is the only one that combines a randomized trial design to evaluate DOTS within methadone clinics. In addition, this study could evaluate the effect of DOT in improving adherence among those who already have viral suppression and are usually not considered candidates for DOT.

12 methadone maintenance clinics administered by university-affiliated medical centers in the New York city; these clinics provide services for approximately 3500 opioid-dependent patients, of whom 10-15% were HIV infected.

Population

HIV-infected opioid users on a stable dose of methadone maintenance, and prescribed ART

Study Design

Two-arm randomized controlled trial

Main Outcomes

The main outcomes were adherence and HIV viral load. Adherence was measured via pill counts (supplemented by information on prescriptions refills, self-reported ingestion, and loss of pills), and by Medication Event Monitoring Systems (MEMS) in which a computerized cap on the medication bottle recorded each opening and a presumptive dose. Adherence was calculated as pills taken divided by pills prescribed during the previous week.

Methods

Participants were recruited from methadone clinic waiting rooms, and were enrolled if they were HIV infected, were prescribed ART, were receiving HIV care at the methadone clinic or affiliated site, had a 5- or 6-day methadone pick-up schedule, and were on a stable dose of methadone for at least 2 weeks. Patients were tested for genotypic resistance to their ART; only those sensitive to their regimen were enrolled. Patients were randomized to either DOT or treatment as usual, and were block-stratified by once versus twice-daily ART regimen. Those in the DOT arm received one dose of ART at the same time they received their daily methadone. Non-observed ART included evening doses for those on twice-daily regimens, some Saturday and all Sunday doses. Participants in the treatment-as-usual (TAU) group received ART prescriptions from their regular HIV providers. All trial participants received adherence counseling. Study visits included a baseline visit and 8 weekly visits, followed by 4 monthly visits, for a total follow-up time of 24 weeks. Adherence was measured at each visit. Plasma HIV viral load (VL) was quantified at baseline, at weeks 8, 16, and 24. Survey information was collected using audio computer-assisted self-interview (ACASI) technology. Trial analysis was based on intent-to-treat approach. Mixed effects models were used to fit repeatedly measured outcomes and to determine the odds of achieving outcomes in the DOT versus TAU arms.

Results

From 2004-2007, 3231 methadone clients were screened; 97 were eligible, and 77 were enrolled and randomized. Baseline characteristics were similar between groups. Study retention was 84% at 24 weeks; 53% of participants were male, 45% Latino and 40% of African heritage; mean age was 47 yrs and the median time on methadone was 10 yrs. All were ART-experienced, 45% had undetectable (<75 copies/ml) VL at baseline; 55% had urine toxicology indicating cocaine use and 31% revealed non-methadone opioid use. At all follow-up assessments, adherence in the DOT group was higher than in the TAU group, including when differences were stratified by baseline VL. The differences in adherence between the two groups was approximately 12% at week 4 (about 75% in the TAU group, and 87% in the DOT group), and 30% at week 24 (55% adherence versus 85% adherence, TAU versus DOT respectively). Over the study period, VL in the DOT group decreased, while VL in the TAU group remained relatively stable. At week 24, the odds of having undetectable VL were 3-fold greater for DOT than TAU participants (OR=3.1, 95% CI: 1.1,5.4). Among DOT participants, the proportion with undetectable VL increased from 51% at baseline to 71% at week 24; among TAU participants, approximately 42% had undetectable VL at both baseline and 24 weeks. Among TAU participants with undetectable baseline VL, 21% became detectable sometime during follow-up.

Conclusions

The authors conclude that DOT for ART can improve HIV treatment adherence as well as viral load among long term methadone-maintenance users. Even among those with undetectable baseline VL and who are not usually considered candidates for DOT, directly observed therapy improves adherence. Thus DOT can be an effective intervention for helping to achieve viral suppression among drug using populations.

Quality Rating

This was a high-quality study. The authors used a randomized trial design with a well described randomization technique and block randomization. Analysis was by intention-to-treat. However, the authors did not indicate whether the study was blinded (to adherence counselors, researchers or data analysts). There was a relatively high loss to follow-up.

Programmatic Implications

This study adds to several studies that support the use of DOT programs within methadone maintenance clinics. HIV-infected drug users have poorer HIV outcomes, mostly due to poor adherence. DOT should be considered for all eligible drug users. Even with this intervention, however, adherence was poor (only 71%), although better than 41% among those who received ART prescriptions from their regular providers.